RESUMEN
Efficiency of reprogramming of human cells into induced pluripotent stem cells (iPSCs) has remained low. We report that individual adult human CD49f+ long-term hematopoietic stem cells (LT-HSCs) can be reprogrammed into iPSCs at close to 50% efficiency using Sendai virus transduction. This exquisite sensitivity to reprogramming is specific to LT-HSCs, since it progressively decreases in committed progenitors. LT-HSC reprogramming can follow multiple paths and is most efficient when transduction is performed after the cells have exited G0. Sequencing of 75 paired skin fibroblasts/LT-HSC samples collected from nine individuals revealed that LT-HSCs contain a lower load of somatic single-nucleotide variants (SNVs) and indels than skin fibroblasts and accumulate about 12 SNVs/year. Mutation analysis revealed that LT-HSCs and fibroblasts have very different somatic mutation signatures and that somatic mutations in iPSCs generally exist prior to reprogramming. LT-HSCs may become the preferred cell source for the production of clinical-grade iPSCs.
Asunto(s)
Células Madre Hematopoyéticas/metabolismo , Células Madre Pluripotentes Inducidas/metabolismo , Adolescente , Adulto , Reprogramación Celular , Femenino , Voluntarios Sanos , Humanos , Masculino , Persona de Mediana Edad , Adulto JovenRESUMEN
Melanoma is a particularly aggressive type of skin cancer, and its incidence has been increasing steadily since the 1970s. This article will review the extensive epidemiologic data demonstrating that ultraviolet radiation (UVR) exposure, from the sun or artificial tanning beds, is the most important environmental risk factor for melanoma; the multiple detrimental effects of UVR on human skin, including DNA damage through the formation of dimeric photoproducts, gene mutations, oxidative stress, inflammation, and immunosuppression, all of which contribute to melanomagenesis; and the evidence that protection from UVR exposure, whether by melanin or by sunscreen, reduces the risk of developing melanoma.